TRAFs in BAFF-R and CD40 signaling pathways in B lymphocytes. (A) In the absence of stimulation, TRAF3 and TRAF2 promote B cell apoptosis. TRAF3 and TRAF2 constitutively form a complex with cIAP1/2 and NIK, target NIK for K48-linked polyubiquitination and degradation, thereby inhibiting NF-κB2 activation in B cells. (B) BAFF-R and CD40 signaling pathways. Upon ligand engagement, BAFF-R or CD40 recruits TRAF3-TRAF2-cIAP1/2 to membrane rafts, thus allowing NIK accumulation and NF-κB2 activation, leading to B cell survival. In addition, TRAF1, 2, 5 and 6 mediate CD40-induced activation of NF-κB1 and MAPKs.